Role of the heat shock protein family in chlorpromazine-induced cardiotoxicity.

Chlorpromazine (CPZ), a first-generation antipsychotic, is widely used in treating schizophrenia and other psychiatric disorders. However, CPZ is also associated with an increased likelihood of sudden cardiac death, and the underlying mechanisms remain unclear. In our study, we aimed to determine the CPZ-induced changes in some members of the heat shock protein family in rat hearts and further explore the possible mechanisms of CPZ-induced cardiotoxicity. Twenty-four Sprague Dawley rats were randomly divided into three groups (n = 8 per group): control, low dose (33.216 mg/kg) and high dose (94.211 mg/kg). CPZ administration induced hypothermia in rats. Pathological changes, including ischaemia and hypoxia, were observed in rat hearts. Furthermore, the serum levels of cardiac Troponin T (c-TN-T) and brain natriuretic peptide (BNP) were elevated in the CPZ-exposed groups. Meanwhile, the protein and gene expression of HSP70, HSP60, HSP27 and HSP10 significantly differed between the CPZ-exposed and control groups. We conclude that acute CPZ exposure could lead to myocardial injury in rats, in which HSPs might play a crucial role. Further investigations are required to elucidate the underlying mechanisms.

Molecular biomarkers of cantharidin-induced cardiotoxicity in Sprague-Dawley rats: Troponin T, vascular endothelial growth factor and hypoxia inducible factor-1α.

Early diagnosis of cantharidin-induced myocardial injury is the key to reduce the fatality rate in clinical practice. The purpose of the present study was to explore biomarkers that can be used for the prediction and diagnosis of cantharidin-induced myocardial injury. Of 65 male Sprague-Dawley rats weighing 200-230 g, 25 rats were divided into five groups according to the administration dose of cantharidin (0, 1.34, 2.67, 4 and 5.34 mg/kg; n = 5 per group) and the other 40 rats were treated with 2.67 mg/kg cantharidin and divided into nine groups according to the administration time (0, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours; n = 4 per group). Pathological changes of hypoxia, necrosis and inflammation were confirmed in heart samples that were exposed to cantharidin by hematoxylin-eosin staining and overall scores of pathological changes among heart samples in cantharidin exposure groups showed an increasing trend compared with in the control group. Coexpression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and caspase9 was shown in the myocardium by immunofluorescence staining. Western blotting results showed that expression of VEGF, HIF-1α and caspase9 in cantharidin-treated rat hearts showed an increasing trend compared with in the control group. Results of enzyme-linked immunosorbent assay suggested that plasma levels of troponin T (TN-T), VEGF and HIF-1α were elevated at different intervals after cantharidin administration, and VEGF and HIF-1α had a significant linear relationship with TN-T that was verified by multiple linear regression analysis. Preliminary results serve to illustrate that TN-T, VEGF and HIF-1α might be valuable molecular markers in cantharidin-induced myocardial injury and that diagnostic accuracy needs to be studied further.

Effects of Methcathinone Exposure during Prenatal and Lactational Periods on the Development and the Learning and Memory Abilities of Rat Offspring.

This study aimed to investigate the effects of prenatal and lactational methcathinone exposure on the development and the learning and memory abilities of rat offspring using a Sprague-Dawley rat model. Pregnant and lactating rats were administered a consecutive daily dose of methcathinone (0.37 mg/kg) or an equivalent volume of saline by injection on gestational days 7-20 and postnatal days 2-15, respectively. The physical development and neurobehavioral test results of rat pups were recorded throughout the lactation period. Morris water maze (MWM) and novel object recognition (NOR) tests were performed from postnatal day 35 to day 42 to assess the learning and memory abilities of rat offspring in adolescence. The occurrence of hair growth and developments in neurological reflexes, such as improvements in limb grasp, righting reflex, and gait, were delayed in pups after perinatal methcathinone exposure compared with that in the control. Results from MWM and NOR tests indicate that perinatal methcathinone exposure induced deficits in spatial memory, learning ability, and novel object exploration in the adolescent offspring compared with that in the control. The impairment of spatial learning and memory was greater in the prenatal exposure group, while the impairment of novel object exploration was greater in the lactational exposure group. These data show that the prenatal and lactational methcathinone exposure induced the delay of physical and neurological reflex development and impaired learning and memory in rat offspring.